Composition for preventing or treating multiple myeloma comprising novel chromanon compound as active ingredient

Abstract

The present invention provides a novel compound having a chromanone or its ring-opening form, phenylpropenone, as backbone and compositions for the preventing or treating multiple myeloma, comprising the same. The compounds of the invention exhibit significant killing effects against various multiple myeloma cell lines and show in vivo anti-cancer effects that exceed those of lenalidomide, a commercially available immunomodulator widely used in the treatment of multiple myeloma and myelodysplastic syndromes. In addition, the compounds of the invention exhibit a significant synergistic effect when co-administered with the thalidomide or its analog lenalidomide, and thus are useful as an efficient therapeutic agent or therapeutic aid agent composition for multiple myeloma which is an incurable disease.

1 . A compound represented by the following Formula 1 or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein R 1  is C 1 -C 3  alkyl; R 2  is hydrogen or 
       
       
         
           
           
               
               
           
         
          (where n is an integer of 0 to 2); R 3  is hydrogen and R 4  is 
       
       
         
           
           
               
               
           
         
          (where m is an integer of 0 to 2 and A 1  is C 6 -C 10  aryl or 5 to 10-membered heteroaryl unsubstituted or substituted with hydroxy, halogen, C 1 -C 3  alkyl, nitro, or 
       
       
         
           
           
               
               
           
         
          or R 3  and R 4  are bonded to each other to form a 6-membered heterocycloalkyl or heterocycloalkene substituted with C 6 -C 10  aryl or 5 to 10-membered heteroaryl unsubstituted or substituted with hydroxy, halogen or C 1 -C 3  alkyl. 
       
     
     
         2 . The compound or the pharmaceutically acceptable salt of  claim 1 , wherein the heteroaryl is selected from the group consisting of thiophene, furan, benzofuran and quinoline. 
     
     
         3 . The compound or the pharmaceutically acceptable salt of  claim 1 , wherein n is 1 and m is 0. 
     
     
         4 . The compound or the pharmaceutically acceptable salt of  claim 1 , wherein the heterocycloalkyl is oxanone and the heterocycloalkene is dihydropyranone. 
     
     
         5 . The compound or the pharmaceutically acceptable salt of  claim 1 , wherein the compound represented by Formula 1 is a compound represented by the following Formula 2: 
       
         
           
           
               
               
           
         
         wherein R 1  and A 1  are as defined in Formula 1. 
       
     
     
         6 . The compound or the pharmaceutically acceptable salt of  claim 1 , wherein the compound represented by Formula 1 is a compound represented by the following Formula 3: 
       
         
           
           
               
               
           
         
         wherein R 1  is as defined in Formula 1,   is a single- or double bond, A 2  is C 6 -C 10  aryl or 5 to 10-membered heteroaryl unsubstituted or substituted with hydroxy, halogen or C 1 -C 3  alkyl. 
       
     
     
         7 . The compound or the pharmaceutically acceptable salt of  claim 1 , wherein the compound represented by Formula 1 is selected from the group consisting of compounds represented by the following Formula 4 to 33: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         8 . A method for preventing or treating cancer comprising administering a composition comprising a compound or a pharmaceutically acceptable salt thereof of  claim 1 , as an active ingredient, to a subject in need thereof. 
     
     
         9 . The method of  claim 8 , wherein the cancer is multiple myeloma. 
     
     
         10 . The method of  claim 8 , further comprising administering a compound represented by the following Formula 34 or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein B 1  is hydrogen or —NH 2 ,   is a single bond or double bond, and B 2  is hydrogen when   is a single bond, or B 2  is oxygen when   is a double bond. 
       
     
     
         11 . A method for preventing or treating cancer comprising co-administering a compound represented by the following Formula 34 or a pharmaceutically acceptable salt thereof, with a compound or a pharmaceutically acceptable salt thereof of  claim 1  to a subject in need thereof; 
       
         
           
           
               
               
           
         
         wherein B 1  is hydrogen or —NH 2 ,   is a single bond or double bond, and B 2  is hydrogen when   is a single bond, or B 2  is oxygen when   is a double bond. 
       
     
     
         12 . The method of  claim 11 , wherein the cancer is multiple myeloma.